EBF1 nuclear repositioning instructs chromatin refolding to promote therapy resistance in T leukemic cells. [MB157_ChIP-seq]

Purpose: To investigate the mechanisms of 3D genome organization in drug-resistant T-ALL Methods: We used multiple epigenomics, chromatin conformation, and transcriptomic assays to study the mechanisms of chromatin adaptation in GSI-sensitive and GSI-resistant T-ALL Results: We report here that T/B cell lineage determining transcription factors are differentially expressed in GSI-resistant T-ALL cells, driving enhancer switching and genome folding reorganization events to promote GSI-resistance. Conclusions: These observations suggest a general mechanism that diffenrential activity of pioneering factors can be exploited to evade addiction to oncogenic signals. ChIP-seq was performed in MB157 and doxycycline-induced MB157 transduced with pInducer20-TCF1 and -EBF1 in duplicates.